Brough, R., Bajrami, I., Vatcheva, R., Natrajan, R., Reis, J. S., Lord, C. J., Ashworth, A. (2012) APRIN is a cell cycle specific BRCA2-interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer. EMBO JOURNAL, 31 (5). pp. 1160-1176. ISSN 0261-4189

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Abstract

Mutations in BRCA2 confer an increased risk of cancer development, at least in part because the BRCA2 protein is required for the maintenance of genomic integrity. Here, we use proteomic profiling to identify APRIN (PDS5B), a cohesion-associated protein, as a BRCA2-associated protein. After exposure of cells to hydroxyurea or aphidicolin, APRIN and other cohesin components associate with BRCA2 in early S-phase. We demonstrate that APRIN expression is required for the normal response to DNA-damaging agents, the nuclear localisation of RAD51 and BRCA2 and efficient homologous recombination. The clinical significance of these findings is indicated by the observation that the BRCA2/APRIN interaction is compromised by BRCA2 missense variants of previously unknown significance and that APRIN expression levels are associated with histological grade in breast cancer and the outcome of breast cancer patients treated with DNA-damaging chemotherapy. The EMBO Journal (2012) 31, 1160-1176. doi: 10.1038/emboj.2011.490; Published online 31 January 2012

Item Type:	Article
Authors (ICR Faculty only):	Ashworth, Alan and Lord, Chris and Reis-Filho, Jorge
All Authors:	Brough, R., Bajrami, I., Vatcheva, R., Natrajan, R., Reis, J. S., Lord, C. J., Ashworth, A.
Additional Information:	ISI Document Delivery No.: 906JX Times Cited: 0 Cited Reference Count: 62 Brough, Rachel Bajrami, Ilirjana Vatcheva, Radost Natrajan, Rachael Reis-Filho, Jorge S. Lord, Christopher J. Ashworth, Alan Breakthrough Breast Cancer; Cancer Research UK We thank Dr N Siaud and Dr M Jasin for providing DR-GFP. This work was funded by Breakthrough Breast Cancer and Cancer Research UK. Nature publishing group New york
Uncontrolled Keywords:	BRCA2 breast cancer DNA repair sister-chromatid cohesion stalled replication forks double-strand break susceptibility gene brca2 damage response pathways dna-damage saccharomyces-cerevisiae prostate-cancer ovarian-cancer drosophila-melanogaster
Research teams:	Closed research groups > Molecular Pathology ICR divisions > Breast Cancer Research > Gene Function ICR divisions > Molecular Pathology > Gene Function
Depositing User:	Barry Jenkins
Date Deposited:	03 Apr 2012 10:03
Last Modified:	12 Feb 2014 16:15
URI:	http://publications.icr.ac.uk/id/eprint/11480

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